The objective of this proposal is to characterize the contributing factors predisposing to calcium deposition on the blood contacting surface of cardiac assist pumps, a complication which has hampered long term successful implants. These studies were initiated employing the model XI left ventricular assist device (LVAD) fabricated by Thermo-Electron Corporation of Waltham, MA from Dr. William Bernhard's surgical research efforts. Calcification, however, occurs on the lining of all types of pumping devices and on a variety of polymer surfaces including both smooth and textured blood contacting surfaces, the latter promoting the deposition of a stable, biologically compatible pseudoneointima (PNI) lining. To define the calcification process, cellular changes occurring on the polymer within the formed PNI are being examined by light and electron microscopy. In addition, specific biochemical blood material interactions (adsorption of proteins, lipids) which promote calcification and mechanical factors contributing to polymer breakdown and subsequent calcification are being investigated. Results to date indicate osteocalcin, the vitamin K dependent calcium binding protein of bone which is also found in blood, is present in the calcific plaque at significantly high levels. Since Gla-proteins are associated with other pathologic calcification, the project will pursue investigations of its role in mediating calcium deposition in LVAD's by immunochemical techniques. In addition to in vivo bovine LVAD implant studies, an in vitro sterile model XI pumping chamber is being employed which allows selective examination of binding of certain serum components to different polymers with subsequent biochemical and calcium binding measurements. Polymer samples are also being implanted intramuscularly and subcutaneously in calves and rats to allow for controlled removal of implants to study early reactions of in vivo blood material interactions. A thorough understanding of the contributing factors to calcium deposition, both cellular and biochemical, will in the future allow a rational decision for the investigation of the calcification process. Since our results indicated a dystrophic calcification, a detailed investigation of the problem in blood pumps could potentially contribute to a general understanding of tissue dystrophic calcification.